During the past year, we have studied an additional 11 untreated patients with active Hodgkin's disease. The finding of increased numbers of monocytes in the peripheral blood mononuclear cells (PBM) has been strengthened. We have analyzed the phytohemagglutinin (PHA) response at three different concentrations and on 2 different days and found a statistically significant difference in the mean responses on both days for all concentrations. Indomethacin augmented the PHA response of the Hodgkin's PBM. However, the PHA response at all concentrations of PHA on both days remained no higher than 80% of the control response. Despite the augmentation of the Hodgkin's proliferative response by indomethacin, the differences in response between Hodgkin's and control PBM remained statistically different. These data suggested that despite abrogating monocyte inhibitory influences to T-cell mitogenesis, the T-cell response to PHA was still impaired. To determine if the T-cell proliferative response could be normalized, an irradiated Ia+ Epstein-Barr virus transformed B-cell line was added to the PHA-stimulated cultures. The addition of the Ia+ B cells normalized the proliferative response of the Hodgkin's T cells. Thus, the addition of a second activating ligand appeared to generate sufficient lymphokine production to normalize proliferation. The Hodgkin's PBM were shown to produce amounts of LAF equal to the control PBMs. Indomethacin failed to augment LAF production. Since the Hodgkin's PBM contained twice as many monocytes as the control PBM, the data indicate that on a per monocyte basis Hodgkin's monocytes produce less LAF after LPS stimulation. To determine if Hodgkin's T cells could produce T-cell growth factor (TCGF, IL-2), PHA and Ia+ cells were used as stimulators. At all three concentrations of PHA, there was no difference in TCGF production between Hodgkin's and control PBM. Indomethacin augmented TCGF activity by both control and Hodgkin's T cells. Since both proliferation and TCGF production were statistically equivalent in the culture systems utilizing both PHA and Ia+ cells, the implication is that in the system stimulated by PHA alone, the PHA fails to generate sufficient TCGF for the cells to proliferate normally. Addition of indomethacin augmented TCGF activity but not enough to normalize proliferation. Measurement of TCGF production after stimulation by PHA alone yields small amounts of TCGF even by normal T cells. Thus, our ability to assay TCGF activity in PHA alone-stimulated Hodgkin's cultures was limited. Using the monoclonal antibody to the TCGF receptor anti-Tac, preliminary data from several experiments suggest that Hodgkin's T cells fail to generate as many TCGF receptors as do control PBM after PHA stimulation. (MI)